LATUDA Rx

Adults (Monotherapy)

• Approval was based on a 6-week, multicenter, randomized, double-blind, placebo-controlled study of adult patients (mean age of 41.5 years, range 18 to 74) with major depressive episodes associated with bipolar I disorder, with or without rapid cycling, and without psychotic features (N=485).

• Patients were randomized to receive one of two flexible-dose ranges of Latuda (20 to 60mg/day, or 80 to 120mg/day) or placebo.

• The primary endpoint was the change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score at Week 6. The key secondary endpoint was the Clinical Global Impression-Bipolar-Severity of Illness scale (CGI-BP-S).

• At week 6, both doses of Latuda achieved superiority to placebo in reduction of MADRS and CGI-BP-S scores. Overall, the high dose range (80 to 120mg/day) did not provide additional benefit compared with the low dose range (20 to 60mg/day).

Adults (Adjunctive Therapy with Lithium or Valproate)

• Approval was based on a  6-week, multicenter, randomized, double-blind, placebo-controlled study of adult patients (mean age of 41.7 years, range 18 to 72)  with major depressive episodes associated with bipolar I disorder, with or without rapid cycling, and without psychotic features (N=340). Patients who remained symptomatic after treatment with lithium or valproate were randomized to flexibly dosed Latuda 20 to 120 mg/day or placebo.  

• The primary endpoint was the change from baseline in MADRS score at Week 6. The key secondary instrument was the CGI-BP-S scale. 

• At week 6, Latuda was superior to placebo in reduction of MADRS and CGI-BP-S scores as an adjunctive therapy with lithium or valproate.

Pediatric Patients (10 to 17 years)  

• Approval was based on a 6-week, multicenter, randomized, double-blind, placebo-controlled study of pediatric patients (10 to 17 years) with major depressive episode associated with bipolar I disorder, with or without rapid cycling, and without psychotic features (N=343). Patients were randomized to flexibly dosed LATUDA 20 to 80 mg/day or placebo.

• The primary endpoint was the change from baseline in CDRS-R score at Week 6. The key secondary endpoint was the change from baseline in CGIBP-S depression score. 

• At week 6, Latuda was superior to placebo in reduction of CDRS-R total score and CGI-BP-S depression score.

Adults

• Approval was based on five 6-week, placebo-controlled studies in adults with schizophrenia. An active-control arm (olanzapine or quetiapine extended-release) was included in 2 studies to assess assay sensitivity.

• The studies assessed psychiatric signs and symptoms at the end of week 6 by using the following:

• Positive and Negative Syndrome Scale (PANSS), is a multi-item inventory of general psychopathology used to evaluate the effects of drug treatment in schizophrenia. PANSS total scores may range from 30 to 210. 

• Brief Psychiatric Rating Scale derived (BPRSd), derived from the PANSS, is a multi-item inventory primarily focusing on positive symptoms of schizophrenia, whereas the PANSS includes a wider range of positive, negative and other symptoms of schizophrenia. The BPRSd consists of 18 items rated on a scale of 1 (not present) to 7 (severe). BPRSd scores may range from 18 to 126.

• The Clinical Global Impression severity scale (CGI-S) is a clinician-rated scale that measures the subject’s current illness state on a 1- to 7-point scale.

• At week 6, study results are as followed:

• Study 1 - Latuda 40mg or 120mg/day achieved superiority to placebo on the BPRSd total score, and the CGI-S.

• Study 2 - Latuda 80mg/day achieved superiority to placebo on the BPRSd total score, and the CGI-S.

• Study 3 - Latuda 40mg or 120mg/day achieved superiority to placebo on the PANSS total score, and the CGI-S.

• Study 4 - Latuda 80mg/day achieved superiority to placebo on the PANSS total score, and the CGI-S.

• Study 5 - Latuda 80mg or 160mg/day achieved superiority to placebo on the PANSS total score, and the CGI-S.

Adolescents (13-17 years) 

• Approval was based on a 6-week, multicenter, randomized, double-blind, placebo-controlled study of 326 adolescents (13 to 17 years) with schizophrenia. Patients were randomized to receive Latuda (40 or 80 mg/day) or placebo.  

• The primary rating instrument used to assess psychiatric signs and symptoms was the PANSS. The key secondary instrument was the CGI-S.

• At week 6, both doses of Latuda achieved superiority to placebo in reduction of PANSS and CGI-S scores. Overall, the 80mg/day dose did not provide additional benefit compared with the 40mg/day dose.